OPTYMALIZACJA ZŁOŻONEJ TERAPII PACJENTÓW Z PRZEWLEKŁYM ZAPALENIEM TRZUSTKI I ZESPOŁEM METABOLICZNYM
Liliya S. Babinets, Nataliia A. Melnyk, Nataliia O. Shevchenko, Galina M. Sasyk, Olexandr S. Zemlyak,
Olexandra Ye. Kopach, Olga Ye. Fedoriv
State Higher Educational Institution «Ternopil State Medical University by I. Horbachevsky of Ministry of Healthcare of Ukraine», Ternopil, Ukraine
Inroduction: The most common reasons of chronic pancreatitis are alcohol abuse, biliary tract and liver diseases, stomach and duodenum, hyperlipidemia, which is often associated with metabolic syndrome.
The aim: to study the effectiveness of using medicine omega-3 polyunsaturated fatty acids in standard therapy to the correction of lipids and prooxidant-antioxidant disorders in patients with chronic pancreatitis and metabolic syndrome.
Materials and methods: The study included 90 patients with chronic pancreatitis with metabolic syndrome. They were divided into two groups: I group (45 patients) received standard treatment; II group (45 patients) along with baseline therapy received medication omega-3 polyunsaturated fatty acids (Omacor) for 2 capsules (1680 mg) for one month.
Results: After treatment the lipid blood spectrum and prooxidant-antioxidant status have improved.
Conclusions: Adding to the complex therapy of patients with chronic pancreatitis and the metabolic syndrome of the medicine omega-3 polyunsaturated fatty acids helps to improve the lipid and prooxidation-antioxidant status more significantly compared with standard baseline therapy.
Wiad Lek 2018, 71, 2 cz. I, -340
Chronic pancreatitis (CP) is one of the most common, rapidly progressing diseases of the pancreas (increase to 70.0 %) with a high incidence of temporary disability and primary disability (up to 15.0 %). CP is characterized by progressive course of the growth is not functional pancreatic insufficiency and development disturbances in lipid metabolism and oxidative-antioxidant system [1, 2]. These epidemiological data due largely preserving the importance of the main etiological factors CP, alcohol abuse, presence of liver and biliary tract diseases, stomach and duodenal ulcers, hyperlipidemia, a component of atherosclerosis, as well as increased exposure to adverse environmental factors [3, 4].
Violation of lipid metabolism is often associated with the so-called lipid triad: increased levels of very low density lipoprotein (VLDL) or triglycerides (TG), low density atherogenic lipoprotein (LDL), and lowered high density lipoprotein (HDL). This triad is the basis of pathogenesis of atherosclerosis, coronary heart disease, and oxidative stress in general [5, 6]. Lipotoxicity, which is one of the tools of the pathological process in dyslipidemia, associated with insulin resistance, metabolic syndrome (MS) and diabetes mellitus (DM) type 2. In other words, lipid metabolism is a manifestation of MS. According to the results of recent studies, MS of in patients with CP is most often observed in the age range of 40-60 years, its specific gravity is (78.4±2.1) %. Among all patients with CP, the specific gravity of such patients is (12.6±0.6) %. The presence of MS and associated dyslipidemia significantly worsens the prognosis and is one of the risk factors for the occurrence of fatty pancreatic necrosis, due to the increase of dyslipidemia. Such patients die from pancreatic necrosis 5.6 times more often than patients with CP without MS [7, 8, 9].
It has been proved that in patients with CP and MS, activation of peroxide lipid oxidation (PLO) occurs while the development of antioxidant system insufficiency (AOS). Thus, the imbalance in the PLO-AOS system and is a damaging link in the metabolic control chain, which affects the formation and progression of CP. Also, the presence and depth of violations in the PLO-AOS system largely determine the severity of the course of the disease. In oxidative stress free radicals block the metabolism of acinar cells, melt lysosomal granules and zymogen granules, oxidize lipids of cell membranes, resulting in an inflammatory reaction with mast cell cytotoxic degeneration, platelet activation and complement, which in turn activates pancreatic progenesis [10, 11].
It is known that the CP with MS is accompanied by a violation of lipid metabolism (hyperthyroidism and dyslipidemia), the most significant of which is hypertriglyceridemia. Preparations of basic therapy (statins) inhibit the synthesis of cholesterol, while directly reducing the number of LDL. The fractions of TG statins act only through a certain cascade of biochemical transfusion, i.e. indirectly . Omega-3 polyunsaturated fatty acids (PUFAs) can enhance the lipid-lowering effect of statins and directly affect hypertriglyceridemia. The hypolipidemic action of eicosapentaenoic and docosahexaenoic fatty acids is due to their ability to inhibit the activity of enzymes responsible for the synthesis of TG in liver cells. Also, omega-3 PUFAs have anticoagulation, anti-aggregate, anti-inflammatory, antioxidant and immunomodulating effects . Consequently, the use of omega-3 PUFAs in the standard baseline therapy CP with MS is appropriate and pathogenetically justified.
To investigate the effectiveness of course treatment with omega-3 polyunsaturated fatty acids (Omacor) in standard therapy for the correction of lipid and prooxidative antioxidant disorders in patients with CP and MS.
MATERIALS AND METHODS
To achieve this goal, 90 patients were selected from the CP in the stage of remission with MS. They were comparable to the etiological factor, socio-economic conditions and nutrition. Also, the influence of the alcohol factor was excluded. Among patients, there were 46 (51.2 %) male age (49.9±8.7) years and 44 female (48.8 %) age (52.65±6.2) years. The average duration of CP was (12.4±4.3) years, MS – (4.2±1.1) years. Patient examination was carried out with their consent. The study did not include patients with moderate to severe DM requiring insulin, severe arterial hypertension, cancer and somatic illness in the stage of decompensation. The studies meet the requirements of the Helsinki Declaration of the World Medical Association «Ethical principles for medical research involving human subjects as the object of study» opinion of the Committee on bioethics State Higher Educational Institution «Ternopil State Medical University by I. Horbachevsky of Healthcare of Ukraine» № 41/2017.
Depending on the treatment program, the females were divided into two groups: I group (45 patients) received standard protocol treatment (SPT) (creon 25.000 IU during meals, pantoprazole 40 mg once a day and/or domperidone 10 mg 3 times daily, atorvastatin 10 mg in the evening, in the presence of arterial hypertension – ramipril 5 mg in the morning, aspirin 75 mg in the evening, in the presence of DM 2 type – met form 1000 mg 1 time per day); II group (45 patients), in addition to SPT, additionally received a preparation of omega-3 PUFAs (Omakor) for 2 tablets (1680 mg) 1 time per day for one month. The control group consisted of 20 practically healthy persons aged 19 to 46 years, the average age – (32.2±1.8) years. Among them there were 11 (55 %) men and 9 (45 %) women.
The diagnosis of CP was verified on the basis of the generally accepted classification in Ukraine proposed by the Scientific Research Institute of Medical Sciences of Ukraine, which corresponds to the Marseilles-Roman classification according to the «Unified clinical protocol of primary, secondary (specialized) medical care and medical rehabilitation of patients with chronic pancreatitis» approved by Order of the Ministry of Health of Ukraine № 638 dated 10.09.2014. All of the patients under study had a lipid metabolism. The diagnosis of MS was established according to guidelines from the National Heart, Lung and Blood Institute (NHLBI) and the American Heart Association (AHA) when at least 3 of the 5 MS criteria were diagnosed.
The patients of II groups were comparable in age, sex, duration of course and CP, the frequency of diagnostic criteria for MS and previous treatment. Indicators of lipid exchange in blood serum of patients under study were determined according to generally accepted methods. The state of the system of LPO and AOS was judged by levels of malonic aldehyde (MA), superoxide dismutase (SOD), SH-groups, catalase and ceruloplasmin (CP) of blood, which were determined by biochemical methods. All studied parameters were determined twice before and after treatment.
Statistical processing of the received data was performed on a personal computer using standard software packages of Microsoft Excel and with help of the computer program Statistica for Windows version 6.0 (Stat Soft inc., USA).
RESULTS AND DISCUSSIONS
By analyzing the lipid metabolism indices before and after treatment in patients of the two study groups, we determined a statistically significant improvement in the entire spectrum of lipidogram parameters (p<0.05). Patients in II group had a higher percentage of lipidogram rates than patients in I group, indicating the property of omega-3 PUFAs to enhance the hypolipidemic effect of statins (Fig. 1).
In particular, under the influence of treatment, there was a statistically significant reduction in TG levels in both I group and II group patients with respect to these indicators before treatment, however, in patients with II group, who additionally took omega-3 PUFAs, the TG level was 15,70 % lower than in patients I of group (p<0.05). As a result of the treatment, a statistically significant decrease in the levels of LDL and VLDL in the two treatment groups was observed compared with the pre-treatment (p<0.001). It should be noted that the level of LDL and VLDL in patients of ІІ group after treatment was statistically significantly lower than those of I group (p<0.05), which proves a significant hypolipidemic effect of omega-3 PUFAs. The level of common cholesterol (CC) after treatment was also statistically significantly reduced in the two treatment groups compared to the treatment before treatment, but in II group, the decrease was more significant and statistically significant for these parameters in I group (p<0.05).
Concerning HDL, their concentration under the influence of treatment increased in all groups compared to baseline (p<0.05), however, in patients with II group, this increase was 27.48 % higher than that of patients in I group. Atherogenic index (AI) after treatment was statistically significantly reduced in both groups compared with those before treatment (p<0.001). AI after treatment was also more statistically significantly decreased in patients of II group compared with patients in І group (p>0.05), which again proves the direct influence of omega-3 PUFAs on lipid metabolism.
In the study of the state of the indicators of the system of LPO and AOS for the treatment of patients with CP and MS, it was found that the level of MA, as a marker for the intensification of LPA, was significantly higher in the I and II group compared with the control and was accordingly (6.35±0.07) μmol/L and (6.39±0.09) μmol/L. After the treatment, the level of MA in I group significantly decreased by 1.40 μmol/l (22.05 %), whereas in II group, this indicator significantly decreased by 2.22 μmol/l (34.75 %), indicating more significant depression of the pro-oxidant mechanisms under the influence of taking the drug omega-3 PUFAs (Omacor) compared with the results of conventional treatment (Fig. 2).
Also, prior to treatment, there was a significant decrease in the activity of AOS enzymes at the level of SOD (I group – (39.22±0.47) units, II group – (39.52±0.45) units) and SH-groups (I group – (38.55±0.47) mmol/l; II group – (38.52±0.45) mmol/L) in both groups compared to control. After the treatment, a more significant increase in the activity of SOD (by 24.98 %) and an increase in the level of SH-groups (by 15.81 %) in II group was observed, while in the I group, these indices increased slightly and unreliable.
The level of catalase in blood plasma before treatment in I and II groups of patients was significantly higher compared to control ((55.72±1.12) % and (55.77±1.03) % respectively). After treatment, this indicator decreased significantly by 16.22 % in I group and 30.68 % in II group, indicating the regulatory capacity of the PUFAs (Omacor) for AOS. As for the blood pressure level in I and II groups, this indicator was elevated compared to control; after treatment, the level of the CP significantly decreased in the two study groups (13.18 % in I group and 23.48 % in II group), which proved the anti-inflammatory and corrective properties of PUFAs in the studied combined pathology (Fig. 2).
1. Adding to the basic therapy of patients with CP and MS medication omega-3 PUMAs led to a more significant improvement in lipid spectrum (p<0.05) than with standard protocol treatment.
2. Use in the complex treatment of patients with CP and MS medication omega-3 PUMAs (Omacor) contributed to a more reliable regression of prooxidant-antioxidant disorders in comparison with standard conventional therapy.
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The study is a fragment of the planned research work of the Department of Primary health care and general practice – family medicine of the State Higher Educational Institution «Ternopil State Medical University by I. Horbachevsky of Ministry of Healthcare of Ukraine» – «Comorbid conditions in the clinic of internal diseases and family physician practice: predictors of development, early diagnosis, prevention and treatment» (UDC 616.1/4-036-07/-08 state registration number 0106U003338).
ADDRESS FOR CORRESPONDENCE
st. S. Bandery, 92/72, 46013, Ternopil, Ukraine
Figure 1. Percentage reduction of lipid spectrum after treatment in patients with CP and MS
Figure 2. Dynamics of indicators of the PLO-AOS system after treatment in patients with CP and MS in comparison groups